GlaxoSmithKline (GSK) announced that oral Hycamtin® (topotecan hard capsules) have received approval from the European Commission for the treatment of relapsed SCLC. Specifically, topotecan hard capsules are indicated as monotherapy for the treatment of adult patients with relapsed SCLC (PS0-2 [*]) [1] for whom re-treatment with the first-line regimen is not considered appropriate.

Topotecan is already available as an intravenous (IV) injection and the approval of topotecan hard capsules provides physicians and patients with another convenient option.

"The approval of topotecan hard capsules is welcome news for patients and their physicians. Small cell lung cancer is a very aggressive disease and there are limited treatment options after relapse," said Dr. Mary O'Brien, Head of the Lung Cancer Unit at The Royal Marsden Hospital, Surrey, UK. "Topotecan not only improves symptoms and extends the lives of patients, but as it is in capsule form treatment can be started without delay."

"The European approval of topotecan as an oral formulation is good news for patients with relapsed small cell lung cancer across Europe. Topotecan hard capsules provide physicians and patients with an alternative, effective treatment, with the added convenience of being administered orally," said Eddie Gray, President, Pharmaceuticals Europe, GlaxoSmithKline. "The approval of topotecan capsules continues to underscore GSK's commitment to the research and development of therapies to address the unmet medical needs of cancer patients around the world."

Data Submitted

The approval was based on positive results from a Phase III study comparing topotecan hard capsules plus best supportive care (BSC [†]) to BSC alone in patients with relapsed SCLC, in addition to Phase II and Phase III supporting studies.

In the pivotal Phase III multicentre trial, 141 patients with relapsed SCLC not considered as candidates for standard IV therapy were randomised to receive BSC alone [n = 70] or topotecan capsules plus BSC [n = 71]. Topotecan capsules added to BSC were associated with prolonged survival in patients with relapsed SCLC (p = 0.0104, HR = 0.64). Median overall survival for topotecan capsules plus BSC was 25.9 weeks (95% CI, 18.3. to 31.6 weeks) compared to 13.9 weeks (95% CI, 11.1 to 18.6 weeks), indicating a 36% reduction in risk of death for patients who received topotecan capsules plus BSC compared with patients who received BSC alone. [2]

During the Phase III study the most common Grade 3 or 4 toxicities with topotecan capsules were neutropenia, anaemia, thrombocytopenia, nausea, diarrhoea, vomiting, fatigue, and alopecia.2

Supporting Studies Submitted

Supportive efficacy and safety data were provided from a Phase II and a Phase III study, each of which compared topotecan capsules (oral) directly to topotecan (IV) in patients with relapsed sensitive SCLC.

In the Phase III study median survival time was 33.0 weeks (95% CI, 29.1 to 42.4 weeks) in the oral group and 35.0 weeks (95% CI, 31.0 to 37.1 weeks) in the IV group, and both treatments were generally well-tolerated. [3] Safety data were presented for the three efficacy studies mentioned above and for an integrated relapsed lung cancer study population of 682 patients. The safety profile was consistent across all four studies.3, [4], [5], [6]

About Small Cell Lung Cancer (SCLC)

Lung cancer is the third most common cancer in Europe contributing to 12.1% of all cancer cases, but it is the most common cause of death from cancer, with an estimated 334,800 deaths in 2006 (19.7% of total deaths from cancer). [7] About 20 out of every 100 cases diagnosed are SCLC. Of all those diagnosed with SCLC, around one in three have limited (early) disease at the time of diagnosis. Two in three already have extensive (advanced) disease at the time of diagnosis. Of those who have limited disease and have chemotherapy, between 35 - 40% will be alive two years following treatment. People with extensive disease are also treated with chemotherapy, but unfortunately the survival rate is even lower. Most only survive another 10 to 12 months following treatment. [8]

About Hycamtin

Hycamtin (topotecan) is a chemotherapeutic agent that belongs to a class of drugs known as topoisomerase I (topo-I) inhibitors. Topo-I is an enzyme essential for the replication of DNA, and therefore cell division, in both normal and cancer cells. Interaction between topo-I and topotecan results in damage to the cell's cancerous genetic material and the death of dividing cancer cells.6

GSK in Oncology

GSK Oncology is dedicated to producing innovations in cancer that will make profound differences in the lives of patients. Through GSK's revolutionary 'bench to bedside' approach, we are transforming the way treatments are discovered and developed, resulting in one of the most robust pipelines in the oncology sector. Our worldwide research in oncology includes partnerships with more than 160 cancer centres. GSK is closing in on cancer from all sides with a new generation of patient focused cancer treatments in prevention, supportive care, chemotherapy and targeted therapies.

About GlaxoSmithKline

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at gsk.

To access the latest GSK Oncology media materials, visit gskcancermedia

Hycamtin is a trade mark of the GlaxoSmithKline group of companies.

References

[1] Treat J, Huang CH, Lane SR, et al. Topotecan in the treatment of relapsed small cell lung cancer patients with poor performance status. Oncologist. 2004;9:173-181

[2] O'Brien MER, Ciuleanu TE, Tsekov H, et al. Phase III Trial Comparing Supportive Care Alone With Supportive Care With Oral Topotecan in Patients With Relapsed Small-Cell Lung Cancer. J Clin Oncol 2006 24: 5441-5447

[3] Eckardt J, von Pawel J, Pujol JL, et al. Phase III Study of Oral Compared With Intravenous Topotecan As Second-Line Therapy in Small-Cell Lung Cancer. J Clin Oncol 2007 25:2086-2092

[4] von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan Versus Cyclophosphamide, Doxorubicin, and Vincristine for the Treatment of Recurrent Small-Cell Lung Cancer. J Clin Oncol 1999 17: 658-667

[5] Eckardt, J, Von Pawel J, Hainsworth JD, et al. Single agent oral topotecan (PO) versus intravenous topotecan (IV) in patients (pts) with chemosensitive small cell lung cancer (SCLC). An international phase III study. Proc Am Soc Clin Oncol 22: 2003 (abstr 2488)

[6] Oral Hycamtin SmPC, 2008. GSK data on file.

[7] Ferlay J, Autier P, Boniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol. 2007 Mar;18(3):581-92. Epub 2007 Feb 7

[8] News. Eur J of Cancer Care. 2006 15 (2), 110-114

GlaxoSmithKline

View drug information on Hycamtin.